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Androgen deprivation

Jun Hao, Xinpei Ci, Hui Xue, Rebecca Wu, Xin Dong, Stephen Yiu Chuen Choi, Haiqing He, Yu Wang, Fang Zhang, Sifeng Qu, Fan Zhang, Anne M Haegert, Peter W Gout, Amina Zoubeidi, Colin Collins, Martin E Gleave, Dong Lin, Yuzhuo Wang
BACKGROUND: Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. OBJECTIVE: To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. DESIGN, SETTING, AND PARTICIPANTS: Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers...
March 12, 2018: European Urology
Munveer S Bhangoo, Brian Cheng, Gregory P Botta, Phataraporn Thorson, Michael P Kosty
As with other genitourinary malignancies, a variety of paraneoplastic syndromes have been revealed to occur in patients with prostate cancer. Stauffer's Syndrome is a well-described clinical syndrome which manifests via intrahepatic cholestasis in patients with renal cell carcinoma. Less common is intrahepatic cholestasis occurring in association with prostate cancer. The current case report discusses a 67-year-old man presenting with liver failure secondary to intrahepatic cholestasis co-existing with metastatic prostate adenocarcinoma...
April 2018: Molecular and Clinical Oncology
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
Ryuji Yamamoto, Tsuyoshi Osawa, Yusuke Sasaki, Shogo Yamamoto, Motonobu Anai, Kouji Izumi, Yoshihiro Matsumura, Juro Sakai, Hiroyuki Aburatani, Atsushi Mizokami, Tatsuhiko Kodama, Toshiya Tanaka
The non-POU domain-containing octamer binding protein p54nrb /NONO is a multifunctional nuclear protein involved in RNA splicing, processing, and transcriptional regulation of nuclear hormone receptors. Through chromosome copy number analysis via whole-exome sequencing, we revealed amplification of the chromosome Xq11.22-q21.33 locus containing the androgen receptor ( AR ) and NONO genes in androgen-independent, castration-resistant prostate cancer (CRPC)-like LNCaP-SF cells. Moreover, NONO was frequently amplified and overexpressed in patients with CRPC...
February 13, 2018: Oncotarget
L Klotz, A Loblaw, R Siemens, P Ouellette, A Kapoor, M Kebabdjian, L Zhang, F Saad
BACKGROUND: In men initiating intermittent androgen deprivation therapy (IADT), a range of induction durations, between 3 and 12 months, have been employed. OBJECTIVE: To determine if the duration of induction ADT influences the duration of the off treatment interval and the recovery of serum testosterone (T). MANEUVER: This was a prospective, randomized, open label study. Men with biochemical recurrence after local therapy for prostate cancer, with a negative bone scan, were randomized between 4 and 10 months of monthly Degarelix...
March 10, 2018: Journal of Urology
Heloisa H M Della-Colleta, Hernandes F Carvalho
Hyaluronan (HA) has been implicated in tissue remodeling, healing, and tumor growth. This study investigated the variation in hyaluronan content, distribution, and metabolism in the rat ventral prostate in response to androgen deprivation after castration. Hyaluronan synthases (HAS 1-3) and hyaluronidases (Hyal 1-3) mRNA abundance and CD44 (a HA receptor) distribution were assessed by RT-PCR and immunohistochemistry, respectively. The results demonstrated an increasingly concentration, but an overall reduction of HA content...
March 13, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Derek S Tsang, Jennifer M Jones, Osai Samadi, Suhayb Shah, Nicholas Mitsakakis, Charles N Catton, William Jeon, Joshua To, Henriette Breunis, Shabbir M H Alibhai
PURPOSE: To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials...
March 12, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Margaret M Centenera, Luke A Selth, Esmaeil Ebrahimie, Lisa M Butler, Wayne D Tilley
Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
T Steuber, C Jilg, P Tennstedt, A De Bruycker, K Decaestecker, T Zilli, B A Jereczek-Fossa, U Wetterauer, A L Grosu, W Schultze-Seemann, H Heinzer, M Graefen, A Morlacco, R J Karnes, Piet Ost
BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis...
March 9, 2018: European Urology Focus
Matthew R Sydes, Melissa R Spears, Malcolm D Mason, Noel W Clarke, David P Dearnaley, Johann S de Bono, Gert Attard, Simon Chowdhury, Bill Cross, Silke Gillessen, Zaf Malik, Rob Jones, Chris Parker, Alastair W S Ritchie, J Martin Russell, Robin Millman, David Matheson, Claire Amos, Clare Gilson, Alison Birtle, Susannah Brock, Lisa Capaldi, Prabir Chakraborti, Ananya Choudhury, Linda Evans, Daniel Ford, Joanna Gale, Stephanie Gibbs, Duncan Gilbert, Robert Hughes, Duncan McLaren, Jason Lester, Ashok Nikapota, Joe O'Sullivan, Omi Parikh, Clive Peedell, Andrew Protheroe, Sarah M Rudman, Richard Shaffer, Denise Sheehan, Matthew Simms, Narayanan Srihari, Räto Strebel, Santhanam Sundar, Shaun Tolan, David Tsang, Mohini Varughese, John Wagstaff, Mahesh K B Parmar, Nicholas D James
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013...
February 26, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Matthew Utter, Sohag Chakraborty, Limor Goren, Lucas Feuser, Yuan-Shan Zhu, David A Foster
Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells...
March 7, 2018: Cancer Letters
Myong Kim, Cheryn Song, In Gab Jeong, Seung-Kwon Choi, Myungchan Park, Myungsun Shim, Young Seok Kim, Dalsan You, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn
BACKGROUND: Here we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer. METHODS: Patients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression...
March 9, 2018: BMC Cancer
Alicia K Morgans, Yu-Hui Chen, Christopher J Sweeney, David F Jarrard, Elizabeth R Plimack, Benjamin A Gartrell, Michael A Carducci, Maha Hussain, Jorge A Garcia, David Cella, Robert S DiPaola, Linda J Patrick-Miller
Purpose Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone. Methods Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months...
March 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Alessandro Magli, Eugenia Moretti, Annarita Tullio, Gianluca Giannarini, Fabrizio Tonetto, Mauro Urpis, Margherita Crespi, Claudio Foti, Agnese Prisco, Margherita Polsinelli, Gioacchino De Giorgi, Giulia Bravo, Paolo Scalchi, Marco Trovò
OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012...
March 8, 2018: Prostate Cancer and Prostatic Diseases
Sam Egger, Suzanne Hughes, David P Smith, Suzanne Chambers, Clare Kahn, Annette Moxey, Dianne L O'Connell
OBJECTIVE: To assess whether the use of complementary and alternative medicines therapies (CAMs) for prostate cancer and/or its treatment side effects by long-term survivors is associated with selected socio-demographic, clinical, health-related quality-of-life (HRQOL) and/or psychological factors. DESIGN, SETTING AND PARTICIPANTS: The Prostate Cancer Care and Outcomes Study (PCOS) is a population-based cohort study of men with prostate cancer who were aged less than 70 years at diagnosis in New South Wales, Australia...
2018: PloS One
Amar U Kishan, Ryan R Cook, Jay P Ciezki, Ashley E Ross, Mark M Pomerantz, Paul L Nguyen, Talha Shaikh, Phuoc T Tran, Kiri A Sandler, Richard G Stock, Gregory S Merrick, D Jeffrey Demanes, Daniel E Spratt, Eyad I Abu-Isa, Trude B Wedde, Wolfgang Lilleby, Daniel J Krauss, Grace K Shaw, Ridwan Alam, Chandana A Reddy, Andrew J Stephenson, Eric A Klein, Daniel Y Song, Jeffrey J Tosoian, John V Hegde, Sun Mi Yoo, Ryan Fiano, Anthony V D'Amico, Nicholas G Nickols, William J Aronson, Ahmad Sadeghi, Stephen Greco, Curtiland Deville, Todd McNutt, Theodore L DeWeese, Robert E Reiter, Johnathan W Said, Michael L Steinberg, Eric M Horwitz, Patrick A Kupelian, Christopher R King
Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy...
March 6, 2018: JAMA: the Journal of the American Medical Association
Sok Kuan Wong, Nur-Vaizura Mohamad, Putri Ayu Jayusman, Ahmad Nazrun Shuid, Soelaiman Ima-Nirwana, Kok-Yong Chin
Selective estrogen receptor modulators (SERMs) represent a class of drugs that act as agonist or antagonist for estrogen receptor in a tissue-specific manner. The SERMs drugs are initially used for the prevention and treatment of osteoporosis in postmenopausal women. Bone health in prostate cancer patients has become a significant concern, whereby patients undergo androgen deprivation therapy is often associated with deleterious effects on bone. Previous preclinical and epidemiological findings showed that estrogens play a dominant role in improving bone health as compared to testosterone in men...
March 6, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
Carsten Nieder, Ellinor Haukland, Adam Pawinski, Jan Norum
Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases)...
March 5, 2018: Medical Oncology
Johnny R Ramroop, Mark N Stein, Justin M Drake
Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach...
2018: Frontiers in Oncology
Christopher J D Wallis, Raj Satkunasivam, Sender Herschorn, Calvin Law, Arun Seth, Ronald T Kodama, Girish S Kulkarni, Robert K Nam
BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cardiovascular risk factors and the development of cardiovascular disease in men with metastatic prostate cancer. We sought to examine the effect of ADT on nonprostate cancer mortality among patients with nonmetastatic prostate cancer. METHODS: We performed a population-based, retrospective cohort study of men aged 66 years and older treated with surgery or radiotherapy for nonmetastatic prostate cancer in Ontario, Canada from 2002 to 2009 using administrative datasets (including the Ontario Cancer Registry, Ontario Drug Benefit, and Ontario Health Insurance Plan)...
March 1, 2018: Urologic Oncology
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